Falls are a leading cause of death in the elderly and, in a majority of patients with Parkinson's disease (PD), the leading levodopa-insensitive cause of hospitalization and longterm care. Falling in PD has been attributed to degeneration of forebrain cholinergic neurons that, in interaction with striatal dopamine losses, impairs the cognitive control of balance, gait and movement.
In addition to the disease characterizing motor symptoms reflecting primarily striatal dopamine loss, prominent autonomic, behavioral and cognitive symptoms, including a propensity for falls, indicate that Parkinson's disease (PD) is based on more widespread, multisystemneurodegenerative processes1. Falls in PD patients2,3 and also in the healthy elderly4 are often disabling events5,6. Both exercise-based programs7-9 and the treatment with acetylcholinesterase inhibitors10,11 reduce fall rates in the elderly and PD patients, though an umnet need to further reduce fall propensity remains.
Although falls in patients are associated with numerous risk factors12-14 impairments in the attentional supervision of movement are a major contributing factor, specifically when unfamiliar surfaces and obstacles or secondary tasks challenge gait, balance, and movement control15-22. Gait, balance and movement errors normally evoke compensatory attentional control. However, as the disease process also impacts the brain's attention systems, such compensatory deployment of attentional resources is increasingly unavailable for rescuing movement and preventing falls. Consistent with this view, both degeneration of the basal forebrain (BF) cholinergic projections to telencephalic and thalamic regions—a major attention system of the brain23,24—and of the cholinergic brain stem projections to thalamus and basal ganglia, correlate with low gait speed, freezing of gait and falls in PD patients25-29.
Also in other CNS diseases such as Lewy Body Dementia (LBD), Parasupranuclear Palsy (PSP) and Mutli Systems Atropy (MSA) balance, gait and movement are impaired due to degeneration of cholinergic neurons30.
From the above it is clear that there remains an unmet need for treatment for use in reducing falls in patients with Parkinson's disease as well as in patients with other CNS diseases where degeneration of cholinergic neurons leads to balance, gait and movement impairment. N-(2-(6-fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-tetrafluoropropoxy) benzylamine with the INN name “idalopirdine” (depicted below) is for the first time disclosed in WO 02/078693 and it is a potent and selective 5-HT6 receptor antagonist which has been in clinical development for treating cognition impairment associated with schizophrenia and as a treatment for AD.

In 2012, a clinical study was reported with idalopirdine used in the treatment of Alzheimer's disease (AD). Data demonstrated that Idalopirding plus 10 mg/day of donepezil significantly improved cognitive function in 278 patients with AD compared to placebo plus donepezil, when measured by AD Assessment Scale-cognitive sub-scale (ADAS-cog). Idalopirdine showed positive results in secondary endpoints including measures of global impression and daily living activities compared to donepezil treated patients. A subsequent phase III study has not bee able to confirm the results.
The results included in this patent application have partly been disclosed in an e-publication (doi: 10.111/ejn.13354, published 29 Jul. 2016)31. Further, the Michigan Complex Motor Control Task (MCMCT) that is used for evaluation of treatment impact on falls, gait and movement stoppages has been described in an article by Kucinski et al.32 